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Profound Decrease in Glomerular Arginine Transport by CAT (Cationic Amino Acid Transporter)-1 Contributes to the FLT-1 (FMS-Like Tyrosine Kinase 1) Induced Preeclampsia in the Pregnant Mice
- Source :
- Hypertension (Dallas, Tex. : 1979). 73(4)
- Publication Year :
- 2019
-
Abstract
- Endothelial dysfunction because of nitric oxide inactivation has been suggested to play a role in the pathogenesis of preeclampsia. During pregnancy, L-arginine transport by CAT-1 (cationic amino acid transporter 1), the only transporter for eNOS (endothelial nitric oxide synthase) is inhibited. We hypothesize that maternal arginine deficiency contributes to the development of preeclampsia. Adenovirus-mediated overexpression of sFlt-1 (soluble fms-like tyrosine kinase 1) in virgin and pregnant mice resulted in glomerular endotheliosis, hypertension, and albuminuria. L-arginine prevented the increase in blood pressure and albuminuria in Flt-1 pregnant but not in Flt-1 virgin mice. Flt-1 augmented arginine transport in pregnant but not in virgin dames. Ex vivo inhibition of CAT-2 leaving exclusively CAT-1 activity, decreased arginine transport velocities in Flt-1 animals more prominently in pregnant dames. Phosphorylated CAT-1/CAT-1 increased in pregnant, sFlt-1-pregnant, and sFlt-1 virgin mice. CAT-2 increased in Flt-1-pregnant and Flt-1-virgin dames. L-arginine augmented arginine transport in pregnant and Flt-pregnant mice and prevented the increase in pCAT-1 and CAT-2 expression. Glomerular cGMP (cyclic guanosine monophosphate) generation as a measure of eNOS activity was decreased in all Flt-1 treated animals. L-arginine abolished the decrease in cGMP levels only in Flt-1-pregnant mice. In conclusion, glomerular endothelial NO generation is compromised in Flt-1-pregnant mice because of CAT-1 inhibition induced by a combined effect of pregnancy and preeclampsia which involves: phosphorylation of CAT-1 and induction of CAT-2. These processes contribute to the clinical syndrome of preeclampsia in mice and are prevented by L-arginine.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Arginine
Kidney Glomerulus
030204 cardiovascular system & hematology
Nitric Oxide
Nitric oxide
Preeclampsia
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Pre-Eclampsia
Enos
Pregnancy
Internal medicine
Internal Medicine
medicine
Animals
Endothelium
Endothelial dysfunction
Phosphorylation
Cyclic guanosine monophosphate
reproductive and urinary physiology
Cationic Amino Acid Transporter 1
Arginine transport
Ion Transport
Vascular Endothelial Growth Factor Receptor-1
biology
biology.organism_classification
medicine.disease
Disease Models, Animal
030104 developmental biology
Endocrinology
chemistry
embryonic structures
Pregnancy, Animal
Female
Tyrosine kinase
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 73
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....779904f10b516d67b68e5ac77d5f287b